DESCRIPTION: Progress through various stages of cell cycle requires an ordered array of biochemical complexes exemplified by cyclin-CDK complexes and their CDK inhibitory regulators. HIV-1, the etiological agent of AIDS, requires mitogenic stimulation of quiescent cells induced by cellular stress and/or cytokines for its activation. Such factors and their possible involvement in HIV gene regulation, have recently been shown by the activation of NF-kB through CDK association with coactivator p300. Tat is the key transactivator of HIV-1, which has been shown to be involved in transactivation of HIV and number of cytokine genes. In this proposal preliminary evidence is provided to indicate that Tat stimulates transcription in two distinct stages of cell cycle, one at G1/S and the other at G2. Therefore, the aim of this study is: 1) address the effect of Tat on HIV, cyclin A and a host of cytokine genes activated at G1/S and G2, by using functional in vitro transcription assays, and transfections of wild type and mutant plasmids into chemically blocked cells at G1/S or G2. 2) defining which pathway, SP 1 dependent or independent, is responsible for G1/S and G2 activation using a series of immunoprecipitation followed by western blots against transcription factors. It is hoped that by understanding cell cycle events related to Tat activation, one might be able to predict similar findings in other viral activators, related to AIDs pathogenesis.